SDF-1/CXCR4介导生物活性骨软骨仿生支架促MSCs归巢及修复骨软骨缺损的实验研究

骨软骨损伤常见且治疗困难。SDF-1能促进干细胞的归巢，而SDF-1/CXCR4 轴能否在介导生物活性骨软骨支架促进 MSCs 归巢及修复骨软骨缺损过程中发挥重要作用，目前尚不清楚。最近研究表明小分子物质Kartogenin（KGN）能诱导间充质干细胞转变为软骨细胞。本项目拟以丝素蛋白、软骨ECM和纳米羟基磷灰石（Nano-HA）为材料，构建软骨层缓释（SDF-1+KGN）、骨层缓释SDF-1的骨软骨仿生支架，研究新型支架SDF-1的释放动力学及其体内、外募集MSCs的作用；研究缓释KGN的软骨层支架促进MSCs成软骨作用及生物学特性；运用组织工程手段评价此无细胞骨软骨支架动员、募集和迁移MSCs修复骨软骨缺损动物模型的效果，明确SDF-1/CXCR4轴发挥的作用及效能。通过此课题，将获得兼具有“趋化引导”及“成软骨诱导”作用的新型骨软骨支架，并为骨软骨的临床治疗新手段开发提供实验基础。

Osteochondral injuries are common and difficult to treat. Stromal cell-derived factor-1(SDF-1) could promote the homing of stem cells. It is still unclear whether biomimetic and bioactive osteochondral scaffold promotes osteochondral regeneration through stromal cell-derived factor-1/CXCR4-mediated MSCs homing. Recent studies show that small molecule Kartogenin (KGN) could induce mesenchymal stem cells into chondrocytes.The project intends to build a bilayered osteochondral scaffold composed of silk fibroin, cartilage ECM and nano hydroxyapatite (Nano-HA), in which the cartilage layer controlled release of small molecules Kartogenin and SDF-1, and the bone layer controlled release SDF-1. The release kinetic of SDF-1 and the effect of SDF-1 on the raising MSCs in vitro and in vivo would be examined. The chondrogenic effect of the cartilage layer scaffold with slow release KGN would also be researched. Using tissue-engineered method, we would evaluate the effect of this acellular osteochondral scaffold on repairing the osteochondral defect in animal model through mobilization, recruitment and migration of MSCs, and make clear the role and mechanism of SDF-1/CXCR4 axis during the process. Through this study, new chemotactic and chondrogenic osteochondral scaffold would be developed, which will provide the experimental basis for clinical treatment for osteochondral injuries.